Our proposed research has been primarily aimed at testing and examining physical models for enamel demineralization and enamel reactions in general with particular emphasis on those situations that bear on the initiation of dental caries and the actions of therapeutic agents for caries. The general theoretical approach involves quantitatively taking into account the effects of all diffusion processes, all chemical equilibria and reactions, and all other physico- chemical factors. The resulting theoretical relationships for the various models are being compared with demineralization data on both enamel and synthetic minerals suspected of being the important mineral phases in the enamel, e.g., hydroxyapatite, dicalcium phosphate, octacalcium phosphate, fluorapatite, etc. Thus, a rigorous and extensive three-way comparison between enamel and theory, between synthetic mineral and theory, and between synthetic mineral and enamel has been possible. This plan of attack has already yielded significant results. Thus, for example, it has been possible by this approach to determine whether a particular ion or molecule affects the demineralization rate by (1) a typical buffer effect, (2) a common ion effect, (3) the usual ionic strength effect, (4) a surface adsorption barrier effect, (5) new phase formation effects, (6) a solution complexing effect, or by some other route. Bibliographic references: The Kinetics and Mechanisms of Reaction of Tooth Enamel in Buffered Solutions of High Fluoride Concentrations, Arch. Oral Biol., 19, 737 (1974). S. C. Valvani, W. I. Higuchi, and J. J. Hefferren. A Two-Site Model for Human Dental Enamel Dissolution in EDTA, J. Dent. Res., 53, 939 (1974). J. L. Fox, W. I. Higuchi, M. Fawzi, R. C. Hwu, and J. J. Hefferren.